Activity of poloxamer CRL-1072 against drug-sensitive and resistant strains of Mycobacterium tuberculosis in macrophages and in mice

Chinnaswamy Jagannath, Martin R. Emanuele, Robert L. Hunter

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The present experiments evaluated a new, highly refined poloxamer, CRL- 1072, alone and in combination with antibiotics against drug-sensitive and - resistant organisms. In macrophage culture, CRL-1072 reduced the drug concentration inhibiting 99% of control growth of isoniazid (INH) from 10 to 0.15 mg/l (fractional inhibitory concentration=0.07) for a drug-resistant strain. CRL-1072 also increased the susceptibility of drug-resistant strains of Mycobacterium tuberculosis to INH, streptomycin, rifampicin, pyrazinamide, ethambutol, PAS, thiacetazone and ethionamide. Fractional inhibitory concentration values of < 0.5 indicated significant synergistic activity. In studies of acute infection in mice, CRL-1072 was only weakly bacteriostatic when used as a single agent but increased the bactericidal activity of INH, streptomycin, rifampicin, pyrazinamide and clindamycin, but not that of ethambutol. CRL-1072 enhanced the bactericidal activity of streptomycin against a streptomycin resistant strain of M. tuberculosis in a murine infection. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalInternational Journal of Antimicrobial Agents
Volume15
Issue number1
DOIs
StatePublished - Jun 2000
Externally publishedYes

Keywords

  • CRL-1072
  • Drug susceptibility
  • Mycobacterium tuberculosis
  • Poloxamers
  • U937

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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